ArticleJCI insight2019
IRAK4 mediates colitis-induced tumorigenesis and chemoresistance in colorectal cancer.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Therapeutic potentials of plant‑based antioxidants on colorectal cancer: Challenges and perspectives (Review).International journal of oncology · 2025Pooled it
- Integration of Transcriptomics and Mammary Epithelial Cell Models Reveals the Regulatory Mechanism of CXCR1 in E. Coli-Induced Bovine Mastitis.Applied biochemistry and biotechnology · 2026Article
- Toll-like receptors: versatile players in tumor.Frontiers in immunology · 2026Review
- Meeting Report From the 2024 Symposium on IRAK4 in Cancer: Highlights and Clinical Updates.Clinical lymphoma, myeloma & leukemia · 2025Review
- IRAK signaling in cancers: mechanisms, targeting, and clinical implications.Expert opinion on investigational drugs · 2025Review
- Exploring the role of neutrophil extracellular traps in colorectal cancer: Insights from single-cell sequencing.World journal of gastrointestinal oncology · 2025Review
- Identifying functional roles and pathways of shared mutations in canine solid tumors by whole-genome sequencing.PloS one · 2025Article
- Targeting Esophageal Cancer: Promising Drugs for the Clinical Landscape and Key Knowledge Gaps.Drug design, development and therapy · 2025Review
- Article
- Toll-like receptor signalling via IRAK4 affects epithelial integrity and tightness through regulation of junctional tension.Development (Cambridge, England) · 2023Article
- Colitis-associated carcinogenesis: crosstalk between tumors, immune cells and gut microbiota.Cell & bioscience · 2023Review
- IRAK2, an Immune and Radiation-Response Gene, Correlates with Advanced Disease Features but Predicts Higher Post-Irradiation Local Control in Non-Metastatic and Resected Oral Cancer Patients.International journal of molecular sciences · 2023Article
- Suppression of TLR signaling by IRAK-1 and -4 dual inhibitor decreases TPF-resistance-induced pro-oncogenic effects in HNSCC.3 Biotech · 2023Article
- Design of Novel IRAK4 Inhibitors Using Molecular Docking, Dynamics Simulation and 3D-QSAR Studies.Molecules (Basel, Switzerland) · 2022Article
- Nano pom-poms prepared exosomes enable highly specific cancer biomarker detection.Communications biology · 2022Article
- Comprehensive Pan-Cancer Analysis of IRAK Family Genes Identifies IRAK1 as a Novel Oncogene in Low-Grade Glioma.Journal of oncology · 2022Article
- IRAK1 and IRAK4 as emerging therapeutic targets in hematologic malignancies.Current opinion in hematology · 2022Review
- The MK2/Hsp27 axis is a major survival mechanism for pancreatic ductal adenocarcinoma under genotoxic stress.Science translational medicine · 2021Article
- Inhibition of Janus Kinase 1 synergizes docetaxel sensitivity in prostate cancer cells.Journal of cellular and molecular medicine · 2021Article
- Interleukin-1 receptor-associated kinase 4 as a potential biomarker: Overexpression predicts poor prognosis in patients with glioma.Oncology letters · 2021Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
Abstract
Aberrant activation of the NF-κB transcription factors underlies chemoresistance in various cancer types, including colorectal cancer (CRC). Targeting the activating mechanisms, particularly with inhibitors to the upstream IκB kinase (IKK) complex, is a promising strategy to augment the effect of chemotherapy. However, clinical success has been limited, largely because of low specificity and toxicities of tested compounds. In solid cancers, the IKKs are driven predominantly by the Toll-like receptor (TLR)/IL-1 receptor family members, which signal through the IL-1 receptor-associated kinases (IRAKs), with isoform 4 (IRAK4) being the most critical. The pathogenic role and therapeutic value of IRAK4 in CRC have not been investigated. We found that IRAK4 inhibition significantly abrogates colitis-induced neoplasm in APCMin/+ mice, and bone marrow transplant experiments showed an essential role of IRAK4 in immune cells during neoplastic progression. Chemotherapy significantly enhances IRAK4 and NF-κB activity in CRC cells through upregulating TLR9 expression, which can in turn be suppressed by IRAK4 and IKK inhibitors, suggesting a feed-forward pathway that protects CRC cells from chemotherapy. Lastly, increased tumor phospho-IRAK4 staining or IRAK4 mRNA expression is associated with significantly worse survival in CRC patients. Our results support targeting IRAK4 to improve the effects of chemotherapy and outcomes in CRC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.